Characterization of the defect in patients with neuraminidase deficiency at the enzyme level will be made. It is not clear whether the defect involves both neuraminidase active against gangliosides and oligosaccharides and this will be studied using the appropriate substrates. It is also not clear if a specific neuraminidase isozyme is absent or whether several isozymes are involved. Studies in amniotic fibroblasts will also be carried out to determine whether the disease can be diagnosed prenatally. Heterozygote identification and homozygote identification will be attempted using leukocytes as well as fibroblasts. Characterization of the structure of the compounds excreted in the urine of such patients will also be made. Further explorations of the nature of the defect in hexosaminidase A-deficient normal adults will be carried out. One specific experiment that needs to be done is to demonstrate that GM2 activity which is preserved in such patients is identical to hex A, as determined by measurement of the GM2 cleaving enzymes, thermal stability, isoelectric point, and reactivity against specific anti-alpha and anti-beta chain antibodies. These studies will be carried out using enzyme isolated from cultured skin fibroblasts from such individuals to determine whether they are indeed kinetic mutants which retain activity for ganglioside GM2 but not for the 4-methylumbelliferyl substrates. Similar studies will be carried out in patients with AB plus mutations as well. Purification of oligosaccharides containing galactose will be made from the urine and tissues of patients with beta-galactosidase deficiency using these compounds as substrates, in an attempt to determine the relationship between enzymatic defect and phenotype in patients with pleotrophic manifestations of GM1 beta-galactosidase deficiency.